Upregulation of AT2 receptor and iNOS impairs angiotensin II-induced contraction without endothelium influence in young normotensive diabetic rats.
作者： Jin Hee Lee , Shichao Xia , Louis Ragolia
DOI: 10.1152/AJPREGU.00191.2008
关键词:
摘要: Diabetes and insulin resistance are associated with an increased risk of hypertension cardiovascular disease. Recent evidence demonstrates that AT2 receptors (AT2R) play important role in the hemodynamic control by vasodilation. The quantitative significance AT2R establishment diabetic vascular dysfunction, however, is not well defined needs further investigation. Goto-Kakizaki (GK) rats, a polygenic model spontaneous normotensive type 2 diabetes, were used to examine any abnormalities function at early stage disease without endothelium influence. Using myograph measure isometric force, we observed ANG II-induced contraction was impaired denuded GK aorta compared Wistar-Kyoto (WKY) exhibited retarded AT1R antagonist response enhanced Rho kinase signaling. When blocked, II induced significant vasodilation precontracted via AT2R. protein mRNA aorta. Blocking restored vasculature levels, demonstrating counteractive for AT1R-induced contraction. Inhibition inducible nitric oxide synthase (iNOS) NG-monomethyl-L-arginine mimicked inhibition aorta, suggesting AT2R-induced dependent on iNOS/NO generation. iNOS also In conclusion, these results clearly demonstrate iNOS-induced, NO-mediated impair endothelium-independent manner diabetes.
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